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NM_000466.3(PEX1):c.1239+1G>T AND Peroxisome biogenesis disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 19, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001526999.1

Allele description [Variation Report for NM_000466.3(PEX1):c.1239+1G>T]

NM_000466.3(PEX1):c.1239+1G>T

Gene:
PEX1:peroxisomal biogenesis factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q21.2
Genomic location:
Preferred name:
NM_000466.3(PEX1):c.1239+1G>T
HGVS:
  • NC_000007.14:g.92517275C>A
  • NG_008341.2:g.16257G>T
  • NM_000466.3:c.1239+1G>TMANE SELECT
  • NM_001282677.2:c.1239+1G>T
  • NM_001282678.2:c.615+1G>T
  • NC_000007.13:g.92146589C>A
  • NM_000466.2:c.1239+1G>T
Nucleotide change:
IVS5, G-T, +1
Links:
OMIM: 602136.0008; dbSNP: rs756876301
NCBI 1000 Genomes Browser:
rs756876301
Molecular consequence:
  • NM_000466.3:c.1239+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001282677.2:c.1239+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001282678.2:c.615+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Peroxisome biogenesis disorder (PBD, ZSS)
Synonyms:
PEROXISOME BIOGENESIS DISORDER (NEONATAL ADRENOLEUKODYSTROPHY/INFANTILE REFSUM DISEASE); INFANTILE PHYTANIC ACID STORAGE DISEASE; PEROXISOME BIOGENESIS DISORDER (NALD/IRD); See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0019234; MedGen: C1832200; OMIM: PS214100

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001737802Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(May 19, 2021) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.

Yik WY, Steinberg SJ, Moser AB, Moser HW, Hacia JG.

Hum Mutat. 2009 Mar;30(3):E467-80. doi: 10.1002/humu.20932.

PubMed [citation]
PMID:
19105186
PMCID:
PMC2649967

Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder.

Ebberink MS, Mooijer PA, Gootjes J, Koster J, Wanders RJ, Waterham HR.

Hum Mutat. 2011 Jan;32(1):59-69. doi: 10.1002/humu.21388.

PubMed [citation]
PMID:
21031596
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001737802.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: PEX1 c.1239+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5 splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251132 control chromosomes (gnomAD). c.1239+1G>T has been reported in the literature in individuals affected with Zellweger Syndrome Spectrum disorders (e.g. Yik_2009, Ebberink_2011, Ratbi_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024